crossing96/oncoscreening huggingface dataset:
Induction of centrosome amplification and chromosome instability in human bladder cancer cells by p53 mutation and cyclin E overexpression.	Centrosome amplification frequently occurs in human cancers and is a major cause of chromosome instability (CIN). In mouse cells, centrosome amplification can be readily induced by loss or mutational inactivation of p53. In human cells, however, silencing of endogenous p53 alone does not induce centrosome amplification or CIN, although high degrees of correlation between p53 mutation and CIN/centrosome amplification in human cancer can be detected, suggesting the presence of additional regulatory mechanism(s) in human cells that ensures the numeral integrity of centrosomes and genomic integrity. Cyclin E, a regulatory subunit for CDK2 that plays a key role in centrosome duplication, frequently is overexpressed in human cancers. We found that cyclin E overexpression, together with loss of p53, efficiently induces centrosome amplification and CIN in human bladder cancer cells but not by either cyclin E overexpression or loss of p53 alone. We extended these findings to bladder cancer specimens and found that centrosome amplification is strongly correlated with concomitant occurrence of cyclin E overexpression and p53 inactivation but not with either cyclin E overexpression or p53 inactivation alone. Because cyclin E expression is strictly controlled in human cells compared with mouse cells, our findings suggest that this stringent regulation of cyclin E expression plays an additional role underlying numeral homeostasis of centrosomes in human cells and that deregulation of cyclin E expression, together with inactivation of p53, results in centrosome amplification.	bladder
Molecular serological diagnosis in transitional cell bladder cancer.	"There are no reliable serological tumor markers for transitional cell carcinoma (TCC) of the urinary bladder. Fluorescent microsatellite analysis (MSA) was used to detect serum-DNA alterations in patients with bladder cancer. Prospectively, fresh tumor-, peripheral blood-, and serum-specimens were collected from 58 consecutive patients treated for TCC of the bladder to obtain the corresponding DNA. DNA was extracted by the phenol-chloroform method from tumors and blood lymphocytes. Serum DNA was isolated by a commercial kit. Fluorescent MSA was performed with a total of 17 polymorphic markers from chromosomal regions 5q, 8p, 9p, 9q, 13q, 14q, 17p, 17q, and 20q in the 58 cancer specimens as well as in specimens from 20 healthy controls. Detection of allelic imbalance and loss of heterozygosity in the tumor and serum specimens was carried out on an automated laser sequencer. Serum-DNA alterations were identified in 79.3% (46/58). Four healthy controls displayed serum-DNA artefacts rendering a specificity of 80%. The highest frequency of serum-DNA alterations (38%) was detected for chromosomal region 8p. Chromosomes 5q, 9p, and 20q showed serum-DNA alterations in 20% to 23%. Identification of tumor-specific serum-DNA alterations was stage independent (P >0.05), but was more frequent in high-grade tumors (P = 0.08). To optimize specificity, simultaneous analysis of tumor DNA is advised to rule out artefacts resembling allelic imbalance in MSA of serum DNA. The method then has potential for application as a ""serological marker"" in the follow-up of patients after radical surgical therapy for invasive TCC of the bladder."	bladder
[Intravesial instillation of recombination interferon-alpha and pirarubicin in the prophylaxis of local recurrence after resection of the superficial bladder cancer].	BACKGROUND & OBJECTIVE: Superficial transitional cell carcinoma (TCC) of urinary bladder tends to recur after transurethral surgery. This study was designed to evaluate the effect of interferon-alpha (IFN-alpha)and pirarubicin (THP) on decreasing postoperative recurrence of superficial bladder cancer. METHODS: Recombinant IFN-alpha and THP has been used in clinical study. One week After operation, 68 patients were prospectively enrolled and divided into two groups randomly: IFN-alpha plus THP group and THP group. The protocols of chemoimmunoprophylaxis include 8 weekly and 10 monthly instillation of 3 x 10(7) IU IFN-alpha plus 40 mg THP in 40 ml 5% glucose via catheter. RESULTS: The follow-up period ranged from 6 to 32 months (median 18.2 months). The cytoscopy and cytology with cold cup biopsies had been carried out every 3 months for 2 years. Recurrence after instillation of IFN-alpha combining THP was observed in only 4 cases (12.1%), bladder irritation was found in 4 cases, fatigue in 3 cases, and rash in 1 case as well. Among the 35 cases in THP group, recurrence was found in 8 cases (22.8%), bladder irritation in 5 cases, fatigue in 3 cases. IFN-alpha plus THP yielded better effect than THP alone (P< 0.05),especially in grade 3 and stage PT1 bladder cancer. CONCLUSIONS: IFN-alpha working in coordination with THP would be an effective remedy to prevent the recurrence of bladder cancer. The intravesical IFN-alpha plus THP appears to be more effective against recurrence than THP alone. Further study is needed for side-effect and popularization in such way.	bladder
Laparoscopic assisted radical cystectomy with ileal neobladder: a comparison with the open approach.	PURPOSE: To date, there have been only a few reports regarding the feasibility of the laparoscopic approach to radical cystectomy. In none of these cases has the laparoscopic approach been contrasted with a contemporary cohort of open cystectomy and diversion. Recently, we initiated laparoscopic assisted radical cystoprostatectomy and ileal neobladder (LACINB) wherein the cystoprostatectomy and pelvic lymph node dissections are performed laparoscopically and the reconstructive portion is performed via a 15 cm Pfannenstiel incision. We present and compare our initial series of LACINB with radical cystectomy performed by the open approach (OCINB) during the same period. MATERIALS AND METHODS: Between September 2001 and February 2003, 13 men underwent LACINB and 11 underwent OCINB at our institution. RESULTS: There was no statistically significant difference in operative time, blood loss or complication rates between the LACINB and OCINB groups. However, postoperative analgesic use was significantly less in the LACINB group. Time to start of a liquid diet, solid diet and length of hospitalization were also significantly less in the LACINB group vs the OCINB group. All margins in both groups were negative for bladder cancer, although 1 patient in the LACINB group had an incidentally found prostate cancer with a positive apical margin. CONCLUSIONS: LACINB is a feasible and reproducible procedure, which results in decreased postoperative pain and quicker recovery without a significant increase in operative time. However, longer followup is needed to assess long-term oncological and functional outcomes.	bladder
Phase I pharmacokinetic study of a single intravesical instillation of gemcitabine administered immediately after transurethral resection plus multiple random biopsies in patients with superficial bladder cancer.	PURPOSE: In this phase I study we determined the pharmacokinetic and toxicity profiles of a single intravesical instillation of gemcitabine administered immediately after complete transurethral resection (TUR) plus multiple random biopsies. MATERIALS AND METHODS: Ten patients with superficial bladder cancer clinically staged as Ta/T1 with no carcinoma in situ were included. A single dose of gemcitabine was administered intra-vesically immediately after TUR plus 6 random biopsies. Five patients received 1,500 mg and 5 received 2,000 mg diluted in 100 ml saline. Retention time in the bladder was 60 minutes. Concentrations of gemcitabine and dFdU (2',2'-difluoro-2'-deoxyuridine) were determined by high pressure liquid chromatography assay. RESULTS: Treatment was clinically well tolerated in all patients. Two patients in the 1,500 mg group had minimal hipogastric discomfort and 1 in the 2,000 mg group had grade 1 bladder spasms. There was no remarkable systemic toxicity on hematology or biochemistry at any dose level on day 12 or 30. One patient per dose level showed tumor recurrence on 3-month repeat cystourethroscopy. Mean maximum gemcitabine concentration was 1.8 microg/ml and the mean last AUC was 158 microg/ml*minute. There was large interpatient variability but no significant differences between the 2 dose levels. CONCLUSIONS: Single intravesical instillation of gemcitabine immediately after TUR and multiple random biopsies for superficial bladder cancer are a safe and well tolerated treatment. The favorable toxicity and pharmacokinetic profiles of intravesical gemcitabine support future phase II studies with this agent.	bladder
Urethral 'recurrence' found 14 years after radical cystectomy.	We report a case of transitional cell urethral cancer diagnosed 14 years after radical cystectomy. Traditionally, in the postcystectomy setting, these cancers have been referred to as 'recurrences'. We review the biological models for the oncogenesis of these cancers and propose that they are typically a result of a field cancerization effect, rather than being derived from the same clone responsible for the original urothelial tumor.	bladder
Extrapulmonary small-cell carcinoma: a single-institution experience.	BACKGROUND: Extrapulmonary small-cell carcinoma (EPSCC) has been recognized as a clinicopathological entity distinct from small-cell carcinoma (SCC) of the lung. This study aimed to review the clinical features, therapy and natural course of patients with EPSCC in Oriental single-institution series. METHODS: We retrospectively reviewed the medical records of patients with SCC between September 1995 and December 2002. Study eligibility required that patients had pathologically proven SCC in sites other than lung and normal radiological findings of the chest and normal sputum cytology or negative bronchoscopic findings. RESULTS: Twenty-four patients with EPSCC were identified and primary sites were various: uterine cervix in seven (29%), urinary bladder in five, colon or rectum in three, kidney in two and stomach, esophagus, pancreas, common bile duct, larynx, parotid gland, thymus in one each. Sixteen patients (66.7%) had limited disease (LD) and eight had extensive disease (ED). Patients with ED received mostly platinum-based chemotherapy, for which the response rate was 57%, but showed an aggressive natural history, with median overall survival (OS) of 9.2 months. Patients with LD were treated with a variety of therapeutic modalities. LD SCC of the cervix showed a favorable clinical course, with five patients being disease-free with a median follow-up of 28.4 months. Patients with LD SCC of sites other than cervix had an aggressive course with a median OS of 9.6 months. CONCLUSION: EPSCC was identified in various sites, with the most common primary site being the uterine cervix. Regardless of the primary site or disease stage, EPSCC of sites other than cervix was usually a fatal disease with a discouraging outcome for various treatment modalities.	bladder
The DNA damaging agent VP16 induces the expression of a subset of ligands from the EGF system in bladder cancer cells, whereas none of the four EGF receptors are induced.	Increased activity of the EGF system exerts a cell survival function in the presence of cytotoxic agents. The aim of our investigation was to identify the ligands and receptors from the EGF system, that are induced by the chemotherapeutic DNA damaging agent VP16 in bladder cancer cell lines. By use of real-time RT-PCR assays for all four receptors and six ligands from the EGF system we demonstrate that in HCV29 bladder cancer cells, amphiregulin, HB-EGF, and epiregulin mRNA levels are elevated (more than 100, 5, and 4 fold, respectively) by VP16. The remaining ligands (EGF, TGFalpha and betacellulin) are uninduced. The same was found for T24A bladder cancer cells, except that TGFalpha also was induced. The four receptors were reduced by VP16 in both cell lines. This demonstrates that the induction of the EGF system is mediated by an increased expression of a subset of the ligands, whereas the four receptors are reduced. For amphiregulin and HER1 we investigated with ELISA assays if the effects of VP16 also were observed at the protein level. We found that VP16 increase the amount of amphiregulin peptide both in the cell membrane and the culture medium. Similarly, the reduced EGF receptor mRNA expression correlated with reduced HER1 protein. Several investigations have shown that labile protein factors can be involved in the regulation of stress inducible growth factors and cytokines. We investigated if a labile protein regulates the expression of the subset of ligands that were induced with VP16. Blocking of protein neosynthesis with cycloheximide resulted in induced mRNA expression of exactly the same subset of ligands as observed with VP16 treatment of both HCV29 and T24A cells. This suggests that a labile protein factor regulates either the transcription or degradation of these mRNA's, and it can be speculated that VP16 also operate by inhibiting the activity of this factor. This is further stressed by the observation that combined treatment with cycloheximide and VP16 show no additive effect. In conclusion, we show that a subset of ligands from the EGF system is upregulated by VP16, whereas none of the four receptors are induced. This might represent a physiological response aimed at rescuing the cells.	bladder
"Radiation or chemotherapy cystitis with ""pseudocarcinomatous"" features."	BACKGROUND: The features of radiation or chemotherapy cystitis mimicking invasive urothelial cancer are not widely known. DESIGN: A search of the consultation files from our institution between January 1996 and September 2003 identified 20 patients with bladder biopsies showing cystitis mimicking invasive urothelial cancer. RESULTS: The mean age at diagnosis was 69 years (range, 40-85 years); 80% were males. Complete history was not available in 1 patient. Seventeen patients had a history of pelvic irradiation (15 prostate cancer and 2 endometrial cancer). Two patients had systemic chemotherapy (1 metastatic colon cancer and 1 mixed connective tissue disease). All patients presented with hematuria. The mean time from radiation and/or chemotherapy to presentation was 27 months (range, 0-84 months). All cases showed epithelial proliferation that mimicked invasive cancer within the lamina propria, with marked proliferation seen in 45% of cases. Mild to moderate nuclear pleomorphism was seen in all cases. A characteristic feature was the presence of pseudoinvasive urothelial nests wrapping around the vessels associated with fibrin deposition. Most cases did not show any mitoses (75%). Ulceration was seen in 39% of cases. All cases showed some degree of hemorrhage, fibrin deposition and fibrin thrombi, fibrosis, and acute and chronic inflammation, with hemosiderin identified in 60% of cases. Edema and vascular congestion were common features (95% and 80%, respectively). Thickened vessels and vascular changes associated with radiation injury were identified in 75% of cases. Seventeen patients were followed for a mean of 9 months (range, 0.25-37 months), and none developed bladder cancer. CONCLUSIONS: Radiation or chemotherapy cystitis can show epithelial proliferations that may be confused with invasive urothelial carcinomas. Other findings characteristic of radiation or chemotherapy cystitis, such as hemorrhage, fibrin, and vascular changes, are often seen in association with the epithelial proliferations and are helpful in distinguishing it from invasive cancer. Pathologists must be aware that these changes may be seen with a remote radiation or chemotherapy history, where this information may not be provided or known at the time of the biopsy evaluation.	bladder
Endometrioid carcinoma of the urinary bladder complicating vesical Mullerianosis: a case report and review of the literature.	Endometriosis of the urinary bladder is uncommon, and malignant transformation within vesical endometriosis is extremely rare. Vesical endometriosis and Mullerianosis can cause problems in differential diagnosis with vesical neoplasm, and, conversely, primary vesical neoplasm arising in endometriosis can be difficult to distinguish from secondary vesical involvement. Mullerianosis has rarely been described in the urinary bladder. A case of endometrioid adenocarcinoma of the urinary bladder is reported, which illustrates the difficulties in diagnosis and the importance of morphology and ancillary studies in establishing the correct diagnosis.	bladder
TRIO amplification and abundant mRNA expression is associated with invasive tumor growth and rapid tumor cell proliferation in urinary bladder cancer.	Studies by comparative genome hybridization have suggested that 5p amplification is related to tumor progression in urinary bladder cancer. In this study seven genes (TAS2R, ADCY2, DNAH5, CTNND2, TRIO, ANKH, and MYO10) located to 5p15.31-5p15.1 were analyzed by fluorescence in situ hybridization using a tissue microarray containing samples from tumors and cell lines with known 5p amplification by comparative genome hybridization. Amplification frequency was highest for TRIO, which maps to 5p15.2 and encodes a protein with a putative role in cell-cycle regulation. To further investigate the role of TRIO amplification in bladder cancer, a tissue microarray containing samples from 2317 bladder tumors was used for fluorescence in situ hybridization analysis. TRIO amplification was strongly associated with invasive tumor phenotype, high tumor grade, and rapid tumor cell proliferation (Ki67 LI) (P < 0.0001 each). Only 7 of 456 pTaG1/G2 tumors (1.5%) but 62 of 485 pT1-4 carcinomas (12.8%) had TRIO amplification. TRIO amplification was not associated with poor prognosis. Using a frozen bladder tumor tissue microarray RNA in situ hybridization confirmed that TRIO is up-regulated in amplified tumors. It is concluded that TRIO up-regulation through amplification has a potential role in bladder cancer progression.	bladder
Seminal sparing cystectomy and ileocapsuloplasty: long-term followup results.	PURPOSE: The efficacy of nerve sparing techniques to save potency in cystoprostatectomy is about 50%. This radical surgery may be proposed to young men with normal sexual function. We report the results of a 13-year experience with our innovative seminal sparing cystectomy and bladder replacement to maintain sexual function in such patients. MATERIALS AND METHODS: Seminal sparing cystectomy is a modification of standard radical cystectomy in which the posterior bladder dissection is anterior to the seminal vesicle plane to preserve the vasa deferens, seminal vesicles, prostatic capsule and neurovascular bundles. Ablation of the whole bladder and the prostatic urothelium with surrounding hypertrophic tissue is guaranteed, and injury to the pelvic nerve plexus that provides autonomic innervation to the corpora cavernosa is avoided. From April 1990 to December 2002 we performed 68 procedures in 63 patients (7 of whom were lost to followup) with superficial bladder cancer resistant to conservative therapies (18 patients with stage T1G2 disease, 13 TaG2, 11 T1G3 and 14 TaG3) and in 5 patients with invasive bladder cancer (T2G3) which was monofocal and away from the bladder neck. All patients had normal sexual function. A complete clinical evaluation (with prostate specific antigen [PSA], digital rectal examination and transrectal ultrasound) to exclude concomitant prostate cancer was performed. Average patient age was 49 years and mean followup was 68 months. RESULTS: Normal erectile function was preserved in 58 patients (95%). Complete daytime continence was reached in 58 patients (95%) and nighttime continence was reached in 19 patients (31%). The early postoperative complication rate was 18% and the delayed complication rate was 26.2%. A total of 55 patients (90.2%) are alive and 6 patients (9.8%) died, 5 of cancer progression. High grade prostatic intraepithelial neoplasia was noticed in prostatic specimens in 3 patients and prostatic cancer was noted in 1 patient. These patients had a normal PSA before operation and a serum PSA less than 0.2 ng/ml at a mean followup of 19 months. No positive margins were identified on permanent histological analysis of the specimens, nor were local pelvic recurrences observed. CONCLUSIONS: Our innovative technique is safe, effective and easy to perform. The oncological and functional results obtained with a long followup justify seminal sparing cystectomy as an excellent surgical procedure which can be proposed to some oncological and nononcological cases.	bladder
Primary T1G3 bladder cancer: organ preserving approach or immediate cystectomy?	PURPOSE: In this retrospective nonrandomized study we compared the long-term outcome in patients with newly diagnosed stage T1G3 bladder cancer treated with transurethral resection and bacillus Calmette-Guerin or immediate cystectomy. MATERIALS AND METHODS: Of 121 patients with a median age of 67 years (range 36 to 88) diagnosed with primary T1G3 bladder cancer between 1976 and 1999, 92 were treated by transureteral resection with additional intravesical bacillus Calmette-Guerin and 29 were treated with immediate cystectomy. RESULTS: Of the 92 patients treated with an organ preserving approach 29 remained disease-free, local recurrence developed in 33 (36%) and progression developed in 30 (33%) at a median followup of 6.9 years (range 0.6 to 16.5). Of these 92 patients 27 (29%) underwent deferred cystectomy at a median of 12.9 months (range 4.8 to 136), of whom 10 (37%) with a median postoperative followup of 19 months (range 2 to 173) died of progressive disease with a median survival of 13 months (range 3 to 34) after cystectomy. The majority of patients who died of progressive disease refused cystectomy, were referred too late for cystectomy, were inoperable or had upper urinary tract disease. Six of the 29 patients (21%) undergoing immediate cystectomy had progression at a median of 13.2 months (range 5.5 to 37). Overall and tumor specific survival at 5 years in patients treated with an organ preserving approach was 69% and 80%, and in those treated with immediate cystectomy it was 54% and 69%, respectively. CONCLUSIONS: The results of this analysis demonstrate that the concept of an organ preserving approach is acceptable and spares the bladder in approximately half of the patients with primary T1G3 bladder cancer. Of the patients 30% require deferred cystectomy, making meticulous, close followup mandatory.	bladder
Percutaneous nephroscopic management of upper urinary tract transitional cell carcinoma: recurrence and long-term followup.	PURPOSE: We present long-term results of the percutaneous approach and resection of upper urinary tract transitional cell carcinoma, and we evaluate the prognostic factors related to recurrence. MATERIALS AND METHODS: A total of 34 patients underwent primary percutaneous resection of an upper urothelial tumor. We treated the patients with a superficial tumor that was completely resected macroscopically. Adjuvant topical chemotherapy or immunotherapy was administered. Patients were followed with excretory urography. Ureteroscopy and computerized tomography were obtained when clinically indicated. RESULTS: With a mean followup of 51 months ipsilateral recurrence developed in 41.2%. Median time to recurrence was 24 months. The rate of kidney preservation was 73.5%. Two patients died of the disease. There was a trend of recurrence in patients with multifocal tumors (OR 2.66, 95% CI 0.07-1.92), history of bladder carcinoma in situ (OR 2.4, 95% CI 1.61-3.74), tumor in renal pelvis (OR 6.45, 95% CI 0.01-1.46) and multiple tumor locations (OR 6.53, 95% CI 0.01-1.54). CONCLUSIONS: The percutaneous approach to renal urothelial tumor should be considered a valid option with a good long-term outcome. Recurrence is not uncommon and, as transitional cell carcinoma superficial bladder cancer it may be treated with endourological maneuvers or radical surgery, but with the obligation to a long lasting, strict surveillance.	bladder